This program program is designed to quantitatively evaluate specific drug-radiation combinations for both beneficial and toxic interactions. Furthermore, it is directed toward elucidating the basic biologic principles governing normal tissue and tumor tissue responses to combined modality oncotherapy. Studies include measurements of cell kill and determination of changes in proliferative activity of tumor and normal tissues following chemotherapeutic treatment with drugs, radiotherapeutic treatment with differing fractionation patterns, and combined drug-radiotherapy protocols. Design prescriptions mandated by growth modes and sensitivities of tumors and design proscriptions imposed by toxicity limitations of normal tissues both contribute ultimately to the evolution of efficacious combined mode treatment. Optimization of the therapeutic ratio for given drug-radiation combinations depends to a large extent on the utilization of appropriate kinetically-based paradigms, descriptive of not just relative degrees of cell kill, but also post-treatment activity of surviving cells. The evolution of such concepts in pre-clinical studies provides much of the framework for designing combined modality approaches to the management of human neoplasia.